Multiple sclerosis in Japan: Nationwide surveys over 30 years

by | CIRS

http://www.neurology-asia.org/articles/20082_131.pdf

Comment; Fascinating article published in 2008 in Asia. I suspect there’s a strong dietary and gut microbiome link that the article doesn’t directly address–though it appears that latter birth date is linked–which would be compatible with adoption of western diet and lifestyle. Chronic inflammation is the root of so many illnesses; why not MS as well? We know there’s a strong gut-brain-microbiome link, why couldn’t it involve MS?

Jun-ichi Kira, Takaaki Ishizu, Manabu Osoegawa, and The Research Committee of Neuroimmunological Diseases Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Abstract

There are two different phenotypes of multiple sclerosis (MS) in Asians: opticospinal (OSMS) and conventional (CMS). In Japan, four nationwide surveys of MS have been performed. The first three were in 1972, 1982 and 1989, and we conducted the fourth in 2004. Based on clinically estimated sites of lesions, 1,493 patients with clinically definite MS were classified as having CMS (57.7%), optic-brainstem-spinal MS (5.8%), brainstem-spinal MS (4.6%), OSMS (16.5%), spinal MS (10.6%) or unclassified MS (4.9%). The latest survey revealed the following: a four-fold increase in the estimated number of clinically definite MS patients in 2003 (9,900; crude MS prevalence, 7.7/100,000) compared with 1972; a shift in the peak age at onset from the early 30s in 1989 to the early 20s in 2003; a successive proportional decrease in optic-spinal involvement in clinically definite MS patients; a significant north-south gradient for the CMS/OSMS ratio; after subdivision of the mainland (30-45° North) into northern and southern parts at 37°N, northern-born northern-residents showed a significantly higher CMS/OSMS ratio and higher frequency of brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) than southern-born southern-residents; among northern patients, the absolute numbers of CMS patients and those with Barkhof brain lesions rapidly increased with advancing birth year. Based on MRI findings, MS patients were further subdivided into those with OSMS with or without longitudinally extensive spinal cord lesions extending over three or more vertebral segments (LESCLs) and those with CMS with or without LESCLs. Although disease duration did not differ significantly among the four groups, EDSS scores were significantly higher in patients with LESCLs than in those without, irrespective of OSMS or CMS phenotype. Similar trends were found for the frequencies of bilateral visual loss, transverse myelitis, and marked CSF pleocytosis and neutrophilia. Increased IgG index, frequencies of brain lesions fulfilling the Barkhof criteria and secondary progression were more commonly found in CMS patients than in OSMS patients, while negative brain MRIs were more commonly encountered in OSMS patients than CMS patients, irrespective of the presence of LESCLs. These findings suggest that MS phenotypes are drastically changed by environmental factors, such as latitude and “Westernization”, and that demographic features not only vary based on CMS or OSMS phenotype, but also with the presence or absence of LESCLs

INTRODUCTION

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) caused by a complex interplay between genetic and environmental factors. Although MS is rare in Asians, selective and severe involvement of the optic nerve and spinal cord is characteristic.1 Okinaka et al2 first reported a large series of Japanese patients with demyelinating diseases in 1958, among whom 175 of 270 cases were described as having Devic’s neuromyelitis optica (NMO), and classical MS was rare. Because these authors found many intermediate cases between NMO and classical MS2 , only monophasic NMO has been referred to as NMO, while relapsing NMO is included within the spectrum of MS.3 In Japan, the latter group has been designated as having the opticospinal form of MS (OSMS) and its clinical criteria was proposed in 1996.4 Recently, NMOIgG, a newly identified marker for NMO5 , was also detected in a fraction of Japanese OSMS patients6,7, and OSMS is now postulated to be the same disease as relapsing NMO.8 However, it remains to be elucidated whether MS, OSMS and NMO are distinct diseases or if they form a continuum.7-10 Japanese are suitable for investigating phenotypic alterations over time in genetically homogeneous and geographically isolated populations who have experienced rapid environmental changes. Because nationwide surveys of MS in Japan were performed using essentially identical criteria in 1972, 1982 and 198911-12, we conducted a fourth nationwide survey in 2004 to uncover any phenotypic alterations in MS that have occurred during Japan’s period of rapid “Westernization”.13

CONCLUSION

In conclusion, the temporal changes and geographical differences in MS phenotypes suggest that susceptibility to the CMS phenotype and brain lesion burdens can be altered drastically over a relatively short period and in particular areas by environmental factors. “Westernization”, which is likely to have reinforced the Western MS phenotype, has taken place equally in northern and southern parts of Japan. Nonetheless, the emergence of Western-type MS appears to be happening faster in the north, suggesting that latitude or latitude-related factors could be influential in determining MS phenotypes, even in races resistant to MS. Interestingly, the MRI features characteristic of Western-type and Asiantype MS, namely Barkhof brain lesions and LESCLs, respectively, appeared to be differentially influenced by changes in environmental factors because the former, which are markedly enhanced in northern-born northern-residents, are also augmented by a “Westernized” environment, in which today’s young generation are being raised, while development of the latter is less affected or unaffected by such changes.

Dr. Raymond Oenbrink
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